Sialoperoxidase and myeloperoxidase are the two main peroxidase enzymes found in the oral cavity. Sialoperoxidase is present in salivary secretions and in the biofilms that line the oral surfaces, while myeloperoxidase is abundant in the dento-gingival sulcus area. In the presence of hydrogen peroxide (H
2
O
2
), oral peroxidases catalyze the oxidation of the pseudohalide anion thiocyanate (SCN
−
) to hypothiocyanite (OSCN
−
), a strong oxidant that serves an antimicrobial role. Furthermore, oral peroxidases consume bacteria-produced H
2
O
2
and could help inactivate toxic carcinogenic and genotoxic substances. Numerous
in vitro
studies have reported the antibacterial, antimycotic and antiviral role of peroxidases, suggesting possible applications in oral therapy. However, the use of oral hygiene products incorporating peroxidase systems has not yet been shown to be beneficial for the treatment or prevention of oral infections. This paradox reflects our incomplete knowledge of the physiological role of peroxidases in a complex environment, such as the oral region. While hygiene is crucial for restoring oral microbiota to a symbiotic state, there are no data to suggest that the addition of a peroxidase
per se
can create a dysbiotic state. Recent investigations have associated the presence of peroxidase activity with gram-positive cocci microbial flora, and its insufficiency with dysbiosis has been linked to pathologies, such as caries, periodontitis or infections of the oral mucosa. Therefore, oxidants generated by oral peroxidases appear to be an essential ecological determinant for oral health through the selection of a symbiotic microbiota capable of resisting oxidative stress. The objective of the present review was to update the current knowledge of the physiological aspects and applications of oral peroxidases in clinical practice.